Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-cd9895bd7-dzt6s Total loading time: 0 Render date: 2024-12-27T07:13:03.588Z Has data issue: false hasContentIssue false

6 - How Arousal-Related Neurotransmitter Systems Compensate for Age-Related Decline

from Part I - Models of Cognitive Aging

Published online by Cambridge University Press:  28 May 2020

By
Mara Mather
Edited by
Ayanna K. Thomas  and
Angela Gutchess
Ayanna K. Thomas
Affiliation:
Tufts University, Massachusetts
Angela Gutchess
Affiliation:
Brandeis University, Massachusetts
Get access

Summary

Without brain systems that modulate arousal, we would not be able to have daily sleep-wake cycles, focus attention when needed, experience emotional responses, or even maintain consciousness. Thus, it is not surprising that there are multiple overlapping neurotransmitter systems that control arousal. In aging, most of these systems show decline in basic features such as number of receptors and transporters, and sometimes even in neuron count. These declines have the potential to disrupt basic arousal functions. Compensatory increases in activity in some of these systems allow for maintained levels of circulating neurotransmitters in those systems – but at the cost of reduced dynamic range in arousal responses.

Keywords

Agingarousalneurotransmittersnorepinephrinenoradrenalinedopamineacetylcholineorexinhistaminehomeostasislocus coeruleus
Type
Chapter
Information
The Cambridge Handbook of Cognitive Aging
A Life Course Perspective
 , pp. 101 - 120
Publisher: Cambridge University Press
Print publication year: 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abdulrahman, H., Fletcher, P. C., Bullmore, E., & Morcom, A. M. (2017). Dopamine and memory dedifferentiation in aging. NeuroImage, 153, 211–220. https://doi.org/10.1016/j.neuroimage.2015.03.031CrossRefGoogle ScholarPubMed
Abercrombie, E. D., & Zigmond, M. J. (1989). Partial injury to central noradrenergic neurons: Reduction of tissue norepinephrine content is greater than reduction of extracellular norepinephrine measured by microdialysis. Journal of Neuroscience, 9(11), 4062–4067. https://doi.org/10.1523/JNEUROSCI.09-11-04062.1989Google Scholar
Acheson, A., & Zigmond, M. J. (1981). Short and long term changes in tyrosine hydroxylase activity in rat brain after subtotal destruction of central noradrenergic neurons. Journal of Neuroscience, 1(5), 493–504. https://doi.org/10.1523/JNEUROSCI.01-05-00493.1981Google Scholar
Acheson, A. L., Zigmond, M. J., & Stricker, E. M. (1980). Compensatory increase in tyrosine hydroxylase activity in rat brain after intraventricular injections of 6-hydroxydopamine. Science, 207(4430), 537–540. https://doi.org/10.1126/science.6101509Google Scholar
Adolfsson, R., Gottfries, C. G., Roos, B. E., & Winblad, B. (1979). Postmortem distribution of dopamine and homovanillic acid in human brain, variations related to age, and a review of the literature. Journal of Neural Transmission, 45(2), 81–105. https://doi.org/10.1007/BF01250085Google Scholar
Alexandre, C., Andermann, M. L., & Scammell, T. E. (2013). Control of arousal by the orexin neurons. Current Opinion in Neurobiology, 23(5), 752–759. https://doi.org/10.1016/j.conb.2013.04.008Google Scholar
Almela, M., Hidalgo, V., Villada, C., et al. (2011). Salivary alpha-amylase response to acute psychosocial stress: The impact of age. Biological Psychology, 87(3), 421–429. https://doi.org/10.1016/j.biopsycho.2011.05.008Google Scholar
Arendt, T., Stieler, J. T., & Holzer, M. (2016). Tau and tauopathies. Brain Research Bulletin, 126, 238–292. https://doi.org/10.1016/j.brainresbull.2016.08.018CrossRefGoogle ScholarPubMed
Arranz, B., Blennow, K., Ekman, R., et al. (1996). Brain monoaminergic and neuropeptidergic variations in human aging. Journal of Neural Transmission, 103(1–2), 101–115. https://doi.org/10.1007/BF01292620Google Scholar
Bäckman, L., Lindenberger, U., Li, S. C., & Nyberg, L. (2010). Linking cognitive aging to alterations in dopamine neurotransmitter functioning: Recent data and future avenues. Neuroscience and Biobehavioral Reviews, 34(5), 670–677. https://doi.org/10.1016/j.neubiorev.2009.12.008CrossRefGoogle ScholarPubMed
Birditt, K. S., Tighe, L. A., Nevitt, M. R., & Zarit, S. H. (2017). Daily social interactions and the biological stress response: Are there age differences in links between social interactions and alpha-amylase? Gerontologist, 6, 1114–1125. https://doi.org/10.1093/geront/gnx168Google Scholar
Birren, J. E. (1960). Behavioral theories of aging. In Shock, N. W. (Ed.), Aging: Some social and biological aspects. Washington: American Association for the Advancement of Science.Google Scholar
Birren, J. E., Cunningham, W. R., & Yamamoto, K. (1983). Psychology of adult development and aging. Annual Review of Psychology, 34(1), 543–575. https://doi.org/10.1146/annurev.ps.34.020183.002551Google Scholar
Blouin, A. M., Fried, I., Wilson, C. L., et al. (2013). Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction. Nature Communications, 4, p. 1547. https://doi.org/10.1038/ncomms2461Google Scholar
Boureau, Y. L., & Dayan, P. (2011). Opponency revisited: Competition and cooperation between dopamine and serotonin. Neuropsychopharmacology, 36(1), 74–97. https://doi.org/10.1038/npp.2010.151Google Scholar
Braak, H., Thal, D. R., Ghebremedhin, E., & Del Tredici, K. (2011). Stages of the pathologic process in Alzheimer disease: Age categories from 1 to 100 years. Journal of Neuropathology and Experimental Neurology, 70(11), 960–969. https://doi.org/10.1038/npp.2010.151Google Scholar
Brewerton, T. D., Putnam, K. T., Lewine, R. R. J., & Risch, S. C. (2018). Seasonality of cerebrospinal fluid monoamine metabolite concentrations and their associations with meteorological variables in humans. Journal of Psychiatric Research, 99, 76–82. https://doi.org/10.1016/j.jpsychires.2018.01.004CrossRefGoogle ScholarPubMed
Britt, D. M., & Day, G. S. (2016). Over-prescribed medications, under-appreciated risks: A review of the cognitive effects of anticholinergic medications in older adults. Missouri Medicine, 113(3), 207–214.Google Scholar
Carlsson, A., & Winblad, B. (1976). Influence of age and time interval between death and autopsy on dopamine and 3-methoxytyramine levels in human basal ganglia. Journal of Neural Transmission, 38(3–4), 271–276. https://doi.org/10.1007/BF01249444Google Scholar
Cason, A. M., Smith, R. J., Tahsili-Fahadan, P., et al. (2010). Role of orexin/hypocretin in reward-seeking and addiction: Implications for obesity. Physiology and Behavior, 100(5), 419–428. https://doi.org/10.1016/j.physbeh.2010.03.009CrossRefGoogle ScholarPubMed
Charles, S. T. (2010). Strength and vulnerability integration: A model of emotional well-being across adulthood. Psychological Bulletin, 136(6), 1068–1091. https://doi.org/10.1037/a0021232Google Scholar
Chiodo, L. A., Acheson, A. L., Zigmond, M. J., & Stricker, E. M. (1983). Subtotal destruction of central noradrenergic projections increases the firing rate of locus coeruleus cells. Brain Research, 264(1), 123–126. https://doi.org/10.1016/0006-8993(83)91128-9Google Scholar
Cho, J. R., Treweek, J. B., Robinson, J. E., et al. (2017). Dorsal raphe dopamine neurons modulate arousal and promote wakefulness by salient stimuli. Neuron, 94(6), 1205–1219. https://doi.org/10.1016/j.neuron.2017.05.020Google Scholar
Cools, R., Nakamura, K., & Daw, N. D. (2011). Serotonin and dopamine: Unifying affective, activational, and decision functions. Neuropsychopharmacology, 36(1), 98–113. https://doi.org/10.1038/npp.2010.121Google Scholar
Davies, P., & Maloney, A. (1976). Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet, 308(8000), p. 1403. https://doi.org/10.1016/s0140-6736(76)91936-xGoogle Scholar
Davis, K. L., Mohs, R. C., Marin, D., et al. (1999). Cholinergic markers in elderly patients with early signs of Alzheimer disease. JAMA, 281(15), 1401–1406. https://doi.org/10.1001/jama.281.15.1401Google Scholar
Ding, Y. S., Singhal, T., Planeta‐Wilson, B., et al. (2010). PET imaging of the effects of age and cocaine on the norepinephrine transporter in the human brain using (S, S)‐[11C] O‐methylreboxetine and HRRT. Synapse, 64(1), 30–38. https://doi.org/10.1002/syn.20696Google Scholar
Downs, J. L., Dunn, M. R., Borok, E., et al. (2007). Orexin neuronal changes in the locus coeruleus of the aging rhesus macaque. Neurobiology of Aging, 28(8), 1286–1295. https://doi.org/10.1016/j.neurobiolaging.2006.05.025Google Scholar
Eisdorfer, C. (1968). Arousal and performance: Experiments in verbal learning and a tentative theory. In Talland, G. A. (Ed.), Human Aging and Behavior (pp. 189–216). Cambridge, MA: Academic Press.Google Scholar
Elman, J. A., Panizzon, M. S., Hagler, D. J. Jr., et al. (2017). Task-evoked pupil dilation and BOLD variance as indicators of locus coeruleus dysfunction. Cortex, 97, 60–69. https://doi.org/10.1016/j.cortex.2017.09.025Google Scholar
Elrod, R., Peskind, E. R., DiGiacomo, L., et al. (1997). Effects of Alzheimer’s disease severity on cerebrospinal fluid norepinephrine concentration. American Journal of Psychiatry, 154(1), 25–30. https://doi.org/10.1176/ajp.154.1.25Google Scholar
El‐Sedeek, M., Korish, A., & Deef, M. (2010). Plasma orexin‐A levels in postmenopausal women: Possible interaction with estrogen and correlation with cardiovascular risk status. BJOG: An International Journal of Obstetrics and Gynaecology, 117(4), 488–492. https://doi.org/10.1111/j.1471-0528.2009.02474.xCrossRefGoogle ScholarPubMed
Fagius, J., & Wallin, B. G. (1993). Long-term variability and reproducibility of resting human muscle nerve sympathetic activity at rest, as reassessed after a decade. Clinical Autonomic Research, 3(3), 201–205. https://doi.org/10.1007/BF01826234Google Scholar
Falk, J. L., & Kline, D. W. (1978). Stimulus persistence in CFF: Overarousal or underactivation? Experimental Aging Research, 4(2), 109–123. https://psycnet.apa.org/doi/10.1080/03610737808257134Google Scholar
Fearnley, J. M., & Lees, A. J. (1991). Aging and Parkinson’s disease: Substantia nigra regional selectivity. Brain, 114, 2283–2301. https://doi.org/10.1093/brain/114.5.2283Google Scholar
Fritschy, J. M., & Grzanna, R. (1992). Restoration of ascending noradrenergic projections by residual locus coeruleus neurons: Compensatory response to neurotoxin‐induced cell death in the adult rat brain. Journal of Comparative Neurology, 321(3), 421–441. https://doi.org/10.1002/cne.903210309Google Scholar
Fronczek, R., van Geest, S., Frölich, M., et al. (2012). Hypocretin (orexin) loss in Alzheimer’s disease. Neurobiology of Aging, 33(8), 1642–1650. https://doi.org/10.1016/j.neurobiolaging.2011.03.014Google Scholar
Gabelle, A., Jaussent, I., Hirtz, C., et al. (2017). Cerebrospinal fluid levels of orexin-A and histamine, and sleep profile within the Alzheimer process. Neurobiology of Aging, 53, 59–66. https://doi.org/10.1016/j.neurobiolaging.2017.01.011Google Scholar
Gannon, M., & Wang, Q. (2018). Complex noradrenergic dysfunction in Alzheimer’s disease: Low norepinephrine input is not always to blame. Brain Research, 1702(1), 12–16. https://doi.org/10.1016/j.brainres.2018.01.001Google Scholar
Gilmor, M. L., Erickson, J. D., Varoqui, H., et al. (1999). Preservation of nucleus basalis neurons containing choline acetyltransferase and the vesicular acetylcholine transporter in the elderly with mild cognitive impairment and early Alzheimer’s disease. Journal of Comparative Neurology, 411(4), 693–704. https://doi.org/10.1002/(SICI)1096-9861(19990906)411:4<693::AID-CNE13>3.0.CO;2-DGoogle Scholar
Gottfries, C. G., Gottfries, I., Johansson, B., et al. (1971). Acid monoamine metabolites in human cerebrospinal fluid and their relations to age and sex. Neuropharmacology, 10(6), 665–672. https://doi.org/10.1016/0028-3908(71)90081-5Google Scholar
Gray, S. L., Anderson, M. L., Dublin, S., et al. (2015). Cumulative use of strong anticholinergics and incident dementia: A prospective cohort study. JAMA Internal Medicine, 175(3), 401–407. https://doi.org/10.1001/jamainternmed.2014.7663Google Scholar
Grothe, M., Heinsen, H., & Teipel, S. J. (2012). Atrophy of the cholinergic basal forebrain over the adult age range and in early stages of Alzheimer’s disease. Biological Psychiatry, 71(9), 805–813. https://doi.org/10.1016/j.biopsych.2011.06.019Google Scholar
Haas, H., & Panula, P. (2003). The role of histamine and the tuberomamillary nucleus in the nervous system. Nature Reviews Neuroscience, 4(2), 121–130. https://doi.org/10.1038/nrn1034Google Scholar
Hart, E., & Charkoudian, N. (2014). Sympathetic neural regulation of blood pressure: Influences of sex and aging. Physiology, 29(1), 8–15. https://doi.org/10.1152/physiol.00031.2013Google Scholar
Higuchi, M., Yanai, K., Okamura, N., et al. (2000). Histamine H1 receptors in patients with Alzheimer’s disease assessed by positron emission tomography. Neuroscience, 99(4), 721–729. https://doi.org/10.1016/s0306-4522(00)00230-xGoogle Scholar
Hoogendijk, W. J., Feenstra, M. G., Botterblom, M. H., et al. (1999). Increased activity of surviving locus ceruleus neurons in Alzheimer’s disease. Annals of Neurology, 45(1), 82–91. https://doi.org/10.1002/1531-8249(199901)45:1<82::AID-ART14>3.0.CO;2-TGoogle Scholar
Hunt, N. J., Rodriguez, M. L., Waters, K. A., & Machaalani, R. (2015). Changes in orexin (hypocretin) neuronal expression with normal aging in the human hypothalamus. Neurobiology of Aging, 36(1), 292–300. https://doi.org/10.1016/j.neurobiolaging.2014.08.010Google Scholar
Iqbal, K., Liu, F., & Gong, C.-X. (2016). Tau and neurodegenerative disease: The story so far. Nature Reviews Neurology, 12(1), 15–27. https://doi.org/10.1038/nrneurol.2015.225Google Scholar
Javier Meana, J., Barturen, F., Asier Garro, M., et al. (1992). Decreased density of presynaptic α2‐adrenoceptors in postmortem brains of patients with Alzheimer’s disease. Journal of Neurochemistry, 58(5), 1896–1904. https://doi.org/10.1038/nrneurol.2015.225Google Scholar
Jogeshwar, M., Lao, P. J., Betthauser, T. J., et al. (2018). Human brain imaging of nicotinic acetylcholine α4β2* receptors using [18F]Nifene: Selectivity, functional activity, toxicity, aging effects, gender effects, and extrathalamic pathways. Journal of Comparative Neurology, 526(1), 80–95. https://doi.org/10.1002/cne.24320Google Scholar
Joshi, S., Li, Y., Kalwani, R. M., & Gold, J. I. (2015). Relationships between pupil diameter and neuronal activity in the locus coeruleus, colliculi, and cingulate cortex. Neuron, 89, 1–14. https://doi.org/10.1016/j.neuron.2015.11.028Google Scholar
Kalaria, R., & Andorn, A. (1991). Adrenergic receptors in aging and Alzheimer’s disease: Decreased α2-receptors demonstrated by [3H] p-aminoclonidine binding in prefrontal cortex. Neurobiology of Aging, 12(2), 131–136. https://doi.org/10.1016/0197-4580(91)90051-KGoogle Scholar
Kalaria, R., Andorn, A., Tabaton, M., et al. (1989). Adrenergic receptors in aging and Alzheimer’s disease: Increased β2‐receptors in prefrontal cortex and hippocampus. Journal of Neurochemistry, 53(6), 1772–1781. https://doi.org/10.1111/j.1471-4159.1989.tb09242.xGoogle Scholar
Karrer, T. M., Josef, A. K., Mata, R., et al. (2017). Reduced dopamine receptors and transporters but not synthesis capacity in normal aging adults: A meta-analysis. Neurobiology of Aging, 57, 36–46. https://doi.org/10.1016/j.neurobiolaging.2017.05.006CrossRefGoogle Scholar
Kish, S. J., Shannak, K., Rajput, A., Deck, J. H., & Hornykiewicz, O. (1992). Aging produces a specific pattern of striatal dopamine loss: Implications for the etiology of idiopathic Parkinson’s disease. Journal of Neurochemistry, 58(2), 642–648. https://doi.org/10.1111/j.1471-4159.1992.tb09766.xGoogle Scholar
Klinkenberg, I., Sambeth, A., & Blokland, A. (2011). Acetylcholine and attention. Behavioural Brain Research, 221(2), 430–442. https://doi.org/10.1016/j.bbr.2010.11.033Google Scholar
Koss, M. C. (1986). Pupillary dilation as an index of central nervous system α2-adrenoceptor activation. Journal of Pharmacological Methods, 15(1), 1–19. https://doi.org/10.1016/0160-5402(86)90002-1Google Scholar
Lavi, S., Nevo, O., Thaler, I., et al. (2007). Effect of aging on the cardiovascular regulatory systems in healthy women. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology, 292(2), R788–R793. https://doi.org/10.1152/ajpregu.00352.2006CrossRefGoogle ScholarPubMed
Lee, T.-H., Greening, S. G., Ueno, T., et al. (2018). Arousal increases neural gain via the locus coeruleus–noradrenaline system in younger adults but not in older adults. Nature Human Behaviour, 2(5), 356–366. https://dx.doi.org/10.1038%2Fs41562-018-0344-1Google Scholar
Lemstra, A. W., Eikelenboom, P., & van Gool, W. A. (2003). The cholinergic deficiency syndrome and its therapeutic implications. Gerontology, 49(1), 55–60. https://doi.org/10.1159/000066508Google Scholar
Li, S.-C., & Rieckmann, A. (2014). Neuromodulation and aging: Implications of aging neuronal gain control on cognition. Current Opinion in Neurobiology, 29, 148–158. https://doi.org/10.1016/j.conb.2014.07.009Google Scholar
Liguori, C., Nuccetelli, M., Izzi, F., et al. (2016). Rapid eye movement sleep disruption and sleep fragmentation are associated with increased orexin-A cerebrospinal-fluid levels in mild cognitive impairment due to Alzheimer’s disease. Neurobiology of Aging, 40, 120–126. https://doi.org/10.1016/j.neurobiolaging.2016.01.007Google Scholar
Lipsitz, L. A., Mietus, J., Moody, G. B., & Goldberger, A. L. (1990). Spectral characteristics of heart rate variability before and during postural tilt. Relations to aging and risk of syncope. Circulation, 81(6), 1803–1810. https://doi.org/10.1161/01.cir.81.6.1803Google Scholar
Ma, S., Hangya, B., Leonard, C. S., Wisden, W., & Gundlach, A. L. (2018). Dual-transmitter systems regulating arousal, attention, learning and memory. Neuroscience and Biobehavioral Reviews, 85, 21–33. https://doi.org/10.1016/j.neubiorev.2017.07.009Google Scholar
Mather, M. (in press). The locus coeruleus-norepinephrine system role in cognition and how it changes with aging. In Poeppel, D., Mangun, G., & Gazzaniga, M. (Eds.), The cognitive neurosciences. Cambridge, MA: MIT Press.Google Scholar
Mather, M., & Harley, C. W. (2016). The locus coeruleus: Essential for maintaining cognitive function and the aging brain. Trends in Cognitive Sciences, 20, 214–226. https://doi.org/10.1016/j.tics.2016.01.001Google Scholar
Matsumura, T., Nakayama, M., Nomura, A., et al. (2002). Age-related changes in plasma orexin-A concentrations. Experimental Gerontology, 37(8), 1127–1130. https://doi.org/10.1016/s0531-5565(02)00092-xGoogle Scholar
McEwen, B. S. (2004). Protection and damage from acute and chronic stress – allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders. Annals of the New York Academy of Sciences, 1032, 1–7. https://doi.org/10.1196/annals.1314.001Google Scholar
McGeer, P. L., McGeer, E. G., & Suzuki, J. S. (1977). Aging and extrapyramidal function. Archives of Neurology, 34(1), 33–35. http://dx.doi.org/10.1001/archneur.1977.00500130053010Google Scholar
Meltzer, C. C., Smith, G., DeKosky, S. T., et al. (1998). Serotonin in aging, late-life depression, and Alzheimer’s disease: The emerging role of functional imaging. Neuropsychopharmacology, 18(6), 407–430. https://doi.org/10.1016/S0893-133X(97)00194-2Google Scholar
Motawaj, M., Peoc’h, K., Callebert, J., & Arrang, J.-M. (2010). CSF levels of the histamine metabolite tele-methylhistamine are only slightly decreased in Alzheimer’s disease. Journal of Alzheimer’s Disease, 22(3), 861–871. https://doi.org/10.3233/JAD-2010-100381Google Scholar
Mouton, P. R., Pakkenberg, B., Gundersen, H. J., & Price, D. L. (1994). Absolute number and size of pigmented locus coeruleus neurons in young and aged individuals. Journal of Chemical Neuroanatomy, 7(3), 185–190. https://doi.org/10.1016/0891-0618(94)90028-0CrossRefGoogle Scholar
Nater, U. M., Hoppmann, C. A., & Scott, S. B. (2013). Diurnal profiles of salivary cortisol and alpha-amylase change across the adult lifespan: Evidence from repeated daily life assessments. Psychoneuroendocrinology, 38(12), 3167–3171. https://doi.org/10.1016/j.psyneuen.2013.09.008Google Scholar
Nater, U. M., & Rohleder, N. (2009). Salivary alpha-amylase as a non-invasive biomarker for the sympathetic nervous system: Current state of research. Psychoneuroendocrinology, 34(4), 486–496. https://doi.org/10.1016/j.psyneuen.2009.01.014Google Scholar
Niv, Y., Daw, N. D., Joel, D., & Dayan, P. (2007). Tonic dopamine: Opportunity costs and the control of response vigor. Psychopharmacology, 191(3), 507–520. https://doi.org/10.1007/s00213-006-0502-4Google Scholar
Nixon, J. P., Mavanji, V., Butterick, T. A., et al. (2015). Sleep disorders, obesity, and aging: The role of orexin. Ageing Research Reviews, 20, 63–73. https://doi.org/10.1016/j.arr.2014.11.001Google Scholar
Ohm, T., Busch, C., & Bohl, J. (1997). Unbiased estimation of neuronal numbers in the human nucleus coeruleus during aging. Neurobiology of Aging, 18(4), 393–399. https://doi.org/10.1016/s0197-4580(97)00034-1Google Scholar
Perry, E. K., Gibson, P. H., Blessed, G., Perry, R. H., & Tomlinson, B. E. (1977). Neurotransmitter enzyme abnormalities in senile dementia: Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue. Journal of the Neurological Sciences, 34(2), 247–265. https://doi.org/10.1016/0022-510x(77)90073-9Google Scholar
Peskind, E. R., Wingerson, D., Murray, S., et al. (1995). Effects of Alzheimer’s disease and normal aging on cerebrospinal fluid norepinephrine responses to yohimbine and clonidine. Archives of General Psychiatry, 52(9), 774–782. https://doi.org/10.1001/archpsyc.1995.03950210068012Google Scholar
Pfaff, D. W. (2006). Brain arousal and information theory. Cambridge, MA: Harvard University Press.Google Scholar
Prell, G. D., Khandelwal, J. K., Burns, R. S., LeWitt, P. A., & Green, J. P. (1990). Influence of age and gender on the levels of histamine metabolites and pros-methylimidazoleacetic acid in human cerebrospinal fluid. Archives of Gerontology and Geriatrics, 11(1), 85–95. https://doi.org/10.1016/0167-4943(90)90059-FGoogle Scholar
Rapoport, S. I., Schapiro, M. B., & May, C. (2004). Reduced brain delivery of homovanillic acid to cerebrospinal fluid during human aging. Archives of Neurology, 61(11), 1721–1724. https://doi.org/10.1001/archneur.61.11.1721Google Scholar
Raskind, M. A., Peskind, E. R., Holmes, C., & Goldstein, D. S. (1999). Patterns of cerebrospinal fluid catechols support increased central noradrenergic responsiveness in aging and Alzheimer’s disease. Biological Psychiatry, 46(6), 756–765. https://doi.org/10.1016/s0006-3223(99)00008-6Google Scholar
Raskind, M. A., Peskind, E. R., Veith, R. C., et al. (1988). Increased plasma and cerebrospinal fluid norepinephrine in older men: Differential suppression by clonidine. Journal of Clinical Endocrinology and Metabolism, 66(2), 438–443. https://doi.org/10.1210/jcem-66-2-438Google Scholar
Robinson, D. S. (1975). Changes in monoamine oxidase and monoamines with human development and aging. In Thorbecke, G. J. (Ed.), Biology of Aging and Development (pp. 203–212). Boston, MA: Springer US.Google Scholar
Rodríguez, J. J., Noristani, H. N., & Verkhratsky, A. (2012). The serotonergic system in ageing and Alzheimer’s disease. Progress in Neurobiology, 99(1), 15–41. https://doi.org/10.1016/j.pneurobio.2012.06.010Google Scholar
Satpute, A. B., Kragel, P. A., Barrett, L. F., Wager, T. D., & Bianciardi, M. (2018). Deconstructing arousal into wakeful, autonomic and affective varieties. Neuroscience Letters, 693, 19–28. https://doi.org/10.1016/j.neulet.2018.01.042Google Scholar
Schliebs, R., & Arendt, T. (2011). The cholinergic system in aging and neuronal degeneration. Behavioural Brain Research, 221(2), 555–563. https://doi.org/10.1016/j.bbr.2010.11.058Google Scholar
Seals, D. R., & Esler, M. D. (2000). Human ageing and the sympathoadrenal system. Journal of Physiology, 528(3), 407–417. https://dx.doi.org/10.1111%2Fj.1469-7793.2000.00407.xGoogle Scholar
Spector, R., Snodgrass, S. R., & Johanson, C. E. (2015). A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans. Experimental Neurology, 273, 57–68. https://doi.org/10.1016/j.expneurol.2015.07.027Google Scholar
Strahler, J., Berndt, C., Kirschbaum, C., & Rohleder, N. (2010). Aging diurnal rhythms and chronic stress: Distinct alteration of diurnal rhythmicity of salivary α-amylase and cortisol. Biological Psychology, 84(2), 248–256. https://doi.org/10.1016/j.biopsycho.2010.01.019Google Scholar
Szot, P., Leverenz, J. B., Peskind, E. R., et al. (2000). Tyrosine hydroxylase and norepinephrine transporter mRNA expression in the locus coeruleus in Alzheimer’s disease. Molecular Brain Research, 84(1), 135–140. https://doi.org/10.1016/S0169-328X(00)00168-6Google Scholar
Szot, P., White, S. S., Greenup, J. L., et al. (2006). Compensatory changes in the noradrenergic nervous system in the locus ceruleus and hippocampus of postmortem subjects with Alzheimer’s disease and dementia with Lewy bodies. Journal of Neuroscience, 26(2), 467–478. https://doi.org/10.1523/JNEUROSCI.4265-05.2006Google Scholar
Takagi, H., Morishima, Y., Matsuyama, T., et al. (1986). Histaminergic axons in the neostriatum and cerebral cortex of the rat: A correlated light and electron microscopic immunocytochemical study using histidine decarboxylase as a marker. Brain Research, 364(1), 114–123. https://doi.org/10.1016/0006-8993(86)90992-3Google Scholar
Theofilas, P., Ehrenberg, A. J., Dunlop, S., et al. (2017). Locus coeruleus volume and cell population changes during Alzheimer’s disease progression: A stereological study in human postmortem brains with potential implication for early-stage biomarker discovery. Alzheimer’s and Dementia, 13(3), 236–246. https://doi.org/10.1016/j.jalz.2016.06.2362Google Scholar
Tyree, S. M., & de Lecea, L. (2017). Optogenetic investigation of arousal circuits. International Journal of Molecular Sciences, 18(8), 1773. https://doi.org/10.3390/ijms18081773Google Scholar
Ursin, R. (2002). Serotonin and sleep. Sleep Medicine Reviews, 6(1), 55–67. https://doi.org/10.1053/smrv.2001.0174Google Scholar
Volkow, N. D., Wise, R. A., & Baler, R. (2017). The dopamine motive system: Implications for drug and food addiction. Nature Reviews Neuroscience, 18, 741–752. https://doi.org/10.1038/nrn.2017.130CrossRefGoogle ScholarPubMed
Wada, H., Inagaki, N., Yamatodani, A., & Watanabe, T. (1991). Is the histaminergic neuron system a regulatory center for whole-brain activity? Trends in Neurosciences, 14(9), 415–418. https://doi.org/10.1016/0166-2236(91)90034-rGoogle Scholar
Weinshenker, D. (2018). Long road to ruin: Noradrenergic dysfunction in neurodegenerative disease. Trends in Neurosciences, 41(4), 211–223. https://doi.org/10.1016/j.tins.2018.01.010.Google Scholar
White, M., Courtemanche, M., Stewart, D. J., et al. (1997). Age-and gender-related changes in endothelin and catecholamine release, and in autonomic balance in response to head-up tilt. Clinical Science, 93(4), 309–316. http://doi.org/10.1042/cs0930309Google Scholar
Whitehouse, P. J., Price, D. L., Struble, R. G., et al. (1982). Alzheimer’s disease and senile dementia: Loss of neurons in the basal forebrain. Science, 215(4537), 1237–1239. https://doi.org/10.1126/science.7058341Google Scholar
Winblad, B., Hardy, J., Bäckman, L., & Nilsson, L. G. (1985). Memory function and brain biochemistry in normal aging and in senile dementia. Annals of the New York Academy of Sciences, 444(1), 255–268. https://doi.org/10.1111/j.1749-6632.1985.tb37595.xGoogle Scholar
Wisor, J. P. (2018). Dopamine and wakefulness: Pharmacology, genetics, and circuitry. In Handbook of experimental psychology (pp. 1–15). Berlin: Springer.Google Scholar
Yanai, K., Watanabe, T., Meguro, K., et al. (1992). Age-dependent decrease in histamine H1 receptor in human brains revealed by PET. NeuroReport, 3(5), 433–436. https://doi.org/10.1097/00001756-199205000-00014Google Scholar
Yo, Y., Nagano, M., Nagano, N., et al. (1994). Effects of age and hypertension on autonomic nervous regulation during passive head-up tilt. Hypertension, 23(Suppl.I), 82–86. https://doi.org/10.1161/01.hyp.23.1_suppl.i82Google Scholar
Yoon, H. S., Hattori, K., Ogawa, S., et al. (2017). Relationships of cerebrospinal fluid monoamine metabolite levels with clinical variables in major depressive disorder. Journal of Clinical Psychiatry, 78(8), e947–e956. https://doi.org/10.4088/JCP.16m11144Google Scholar
Yu, X., Ye, Z., Houston, C. M., et al. (2015). Wakefulness is governed by GABA and histamine cotransmission. Neuron, 87(1), 164–178. https://doi.org/10.1016/j.neuron.2015.06.003Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×